Bony fractures are among the most common morbidities affecting breast cancer survivors, particularly postmenopausal breast cancer survivors. There is evidence to suggest that the fracture risk for breast cancer patients is substantially higher than the general population, and that it is likely to worsen in coming years. First, several European studies and the Women's Health Initiative identified an increased fracture risk among breast cancer survivors even in the era when tamoxifen, which may offer some protection against fractures, was the most common hormonal agent. Second, clinical trials in premenopausal women have shown rapid losses in bone density after cytotoxic adjuvant chemotherapy. Evidence is more limited among postmenopausal women, but animal studies and single-center human studies suggest that cytotoxic chemotherapy might also increase their fracture risk. Finally, advances in adjuvant hormonal therapy with the introduction of aromatase inhibitors (AIs) suggest that osteoporosis will become a greater problem in the future. Clinical trials suggest that AIs reduce breast cancer mortality but increase fracture risk by approximately 40%. Given these considerations, we propose to determine the five-year incidence of hip and total nonvertebral fractures among a population-based sample of postmenopausal SEER-Medicare breast cancer survivors compared with age-matched Medicare enrollees. The study will also examine any association of common adjuvant chemotherapy regimens containing methotrexate and anthracyclines with fractures among the same sample of postmenopausal breast cancer survivors. Finally, this study will explore the association of the most commonly used adjuvant hormonal therapies for postmenopausal breast cancer (tamoxifen and aromatase inhibitors) with hip and total nonvertebral fractures among a population-based surveyed cohort of postmenopausal breast cancer survivors. This study will provide effectiveness data regarding the occurrence of osteoporotic fractures in older breast cancer patients and their relationship to initial systemic adjuvant therapies. It will provide important guidance for counseling and treatment initiatives for osteoporosis among breast cancer survivors. Its preliminary findings from a population-based cohort of early aromatase inhibitor users should provide important pilot data for future study into longer-term bone effects of various types of hormonal therapies using Medicare Part D or other administrative data. PUBLIC HEALTH RELEVANCE: Bony fractures are among the most common problems affecting breast cancer survivors, particularly postmenopausal breast cancer survivors. We will investigate the risk of fracture among postmenopausal breast cancer survivors compared with women without breast cancer, and then will explore the contribution of breast cancer treatments (chemotherapy or aromatase inhibitors) to fracture risk. This study should provide importance guidance for counseling and treatment initiatives for osteoporosis among breast cancer survivors. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]